The main objective of this program is to establish a method whereby rational therapies for head injured man can be defined and tested in a scientific manner. This is not presently possible. To accomplish this objective the program is designed to: (1) define the structural, pathophysiologic and metabolic response of the human brain to severe mechanical injury, (2) establish a set of criteria which can provide an accurate prognosis in the head injured patient in the early period following the injury, and (3) define in a controlled animal model the structural, pathophysiological and metabolic response of the brain as a function of force. Multiple rather than single parameters of the brain state must be measured and used to define prognosis. To accomplish objectives 1 and 2 above, a clinical program will study in head injured man: neurological and neuro-ophthalmological examination; intracranial pressure; brain electrical activity; cerebral blood flow status; computerized axial tomography; neurotransmitters and metabolites in cerebrospinal fluid; cardiopulmonary relationships; ultimate result; neuroanatomy and neuropathology at autopsy. Automated data collection, storage and processing will permit definitions of those powerful features which define prognosis. Hypotheses will be tested in each study to provide better understanding of the human brain's response to trauma. To accomplish objective 3 a laboratory program will study multiple parameters in a rat acceleration-deceleration injury model and a well controlled cat fluid percussion model. An ischemia injury model will seek to extract features of this pure injury from mechanical trauma. Brain abnormalities will be defined as a function of force in the following studies: brain electrical activity; ultrastructure and blood brain barrier; neuroanatomy and neuropathology; neurotransmitter integrity; mechanisms in cerebral edema; cerebral microcirculation. Therapeutic programs will then be tested in the laboratory and clinical settings.